Heme Biosynthesis in Methanosarcina barkeri via a Pathway Involving Two Methylation Reactions

Abstract

The methanogenic archaeon Methanosarcina barkeri synthesizes protoheme via precorrin-2, which is formed from uroporphyrinogen III in two consecutive methylation reactions utilizing S-adenosyl-L-methionine. The existence of this pathway, previously exclusively found in the sulfate-reducing ␦-proteobacterium Desulfovibrio vulgaris, was demonstrated for M. barkeri via the incorporation of two methyl groups from methionine into protoheme.

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

“…However, increasing amounts of genome sequencing data started to reveal some interesting insights into heme biosynthesis. In particular, most archaeal genomes were found to be missing orthologs of hemE, hemF or hemN, hemG or hemY, and hemH even though these genomes also encoded a number of hemoproteins, highlighting the fact that they must be able to make heme through some alternative process (176). A similar observation was also made for the genomes of sulfate-reducing bacteria, including that of D. vulgaris (177).…”

“…Moreover, this result demonstrated that the alternative pathway was likely to be much more widespread than previously thought, representing the major pathway for heme synthesis within the archaeal kingdom of life (176). This prompted a more detailed bioinformatic approach in order to help identify the proteins and enzymes associated with the transformation of uroporphyrinogen III into heme within the Archaea.…”

“…It was therefore proposed that heme-requiring archaea may make heme by the alternative heme pathway first put forward by Ishida and colleagues (176). This idea proved to be correct, as when non-covalently bound heme was extracted from cell lysates of Methanosarcina barkeri that had been grown on medium containing L-(methyl-d 3 )methionine and analyzed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry, the data clearly showed that a significant proportion of the deuterated label had been incorporated into heme (176). This finding is consistent with the presence of the alternative heme biosynthetic pathway that had been observed by Ishida et al (46).…”

Controlling the delicate balance of tetrapyrrole biosynthesis

“…The modern haem pathway, as shown in figure 1, might have evolved from a prototype resembling the siro-haem synthesis, which uses only three enzymatic steps from Urogen III via the intermediate precorrin-2 [5]. This is supported by the fact that archaea synthesize haem via the precorrin-2 pathway [27]. Furthermore, precorrin-haem could have evolved from an even earlier corrin-based tetrapyrrole molecule (figure 3a).…”

Tetrapyrrolbiosynthese in denitrifizierenden Bakterien und Archaea

“…euka- ryotischen Syntheseweg unterscheidet. Schon seit Mitte der 1990er-Jahre weiß man, dass dieser "alternative" Hämbiosyntheseweg über das Intermediat Precorrin-2 verläuft [2,7]. Bioinformatische Analysen der Verbreitung der bekannten, für die "herkömmliche" Häm-biosynthese in Bakterien benötigten hemGene zeigten, dass die frühen Hämbiosyn-thesegene hemA, hemL, hemB, hemC und hemD, deren Proteinprodukte für die Bildung von Uroporphyrinogen III verantwortlich sind, in Archaea vorhanden sind [8,9].…”